ArticleNature communications2020
Maintenance of sarcomeric integrity in adult muscle cells crucially depends on Z-disc anchored titin.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 69 citations in OpenAlex.
- Nx3 Is a Z-Disk Structural and Signaling Hub That Is Reduced in Heart Failure.Circulation research · 2026Article
- Klhl41b orchestrates sarcomere assembly and growth to drive skeletal muscle hypertrophy in vivo.Skeletal muscle · 2026Article
- The titin N2A-MARP signalosome constrains muscle longitudinal hypertrophy in response to stretch.eLife · 2026Article
- Myosin Post-Translational Modifications Associated With Critical Illness Myopathy.Acta physiologica (Oxford, England) · 2026Article
- Selective titin cleavage disrupts cardiac mechanical homeostasis to drive heart failure and fibrosis.Nature cardiovascular research · 2026Article
- Mending the Achilles heels of titin in cardiac and musculoskeletal disease.Biophysical reviews · 2026Review
- Fast Myosin Binding Protein-C Is a Vital Regulator in Young and Aged Fast Skeletal Muscle Homeostasis.Journal of cachexia, sarcopenia and muscle · 2025Article
- Mechanically knocking out titin reveals protein tension loss as a trigger of muscle disease.Nature biomedical engineering · 2025Article
- Article
- Genetic and metabolic insights into sexual dimorphism in the flexor carpi radialis of Asiatic toads (Bufo gargarizans) associated with amplexus behavior.BMC genomics · 2025Article
- Modulation of Titin and Contraction-Regulating Proteins in a Rat Model of Heart Failure with Preserved Ejection Fraction: Limb vs. Diaphragmatic Muscle.International journal of molecular sciences · 2024Article
- Allelic heterogeneity of TTNtv dilated cardiomyopathy can be modeled in adult zebrafish.JCI insight · 2024Article
- An optimized approach to study nanoscale sarcomere structure utilizing super-resolution microscopy with nanobodies.PloS one · 2024Article
- Inflammation and Fatty Infiltration Correlates with Rotator Cuff Muscle Atrophy in Hypercholesterolemic Yucatan Microswine.Journal of orthopaedics and sports medicine · 2024Article
- Impaired Cardiac and Skeletal Muscle Energetics Following Anthracycline Therapy for Breast Cancer.Circulation. Cardiovascular imaging · 2023Observational
- Disruption of Z-Disc Function Promotes Mechanical Dysfunction in Human Myocardium: Evidence for a Dual Myofilament Modulatory Role by Alpha-Actinin 2.International journal of molecular sciences · 2023Article
- mNature aging · 2023Article
- Simple and efficient differentiation of human iPSCs into contractible skeletal muscles for muscular disease modeling.Scientific reports · 2023Article
- Article
- Interplay between Nrf2 and αB-crystallin in the lens and heart of zebrafish under proteostatic stress.Frontiers in molecular biosciences · 2023Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The giant protein titin is thought to be required for sarcomeric integrity in mature myocytes, but direct evidence for this hypothesis is limited. Here, we describe a mouse model in which Z-disc-anchored TTN is depleted in adult skeletal muscles. Inactivation of TTN causes sarcomere disassembly and Z-disc deformations, force impairment, myocyte de-stiffening, upregulation of TTN-binding mechanosensitive proteins and activation of protein quality-control pathways, concomitant with preferential loss of thick-filament proteins. Interestingly, expression of the myosin-bound Cronos-isoform of TTN, generated from an alternative promoter not affected by the targeting strategy, does not prevent deterioration of sarcomere formation and maintenance. Finally, we demonstrate that loss of Z-disc-anchored TTN recapitulates muscle remodeling in critical illness 'myosinopathy' patients, characterized by TTN-depletion and loss of thick filaments. We conclude that full-length TTN is required to integrate Z-disc and A-band proteins into the mature sarcomere, a function that is lost when TTN expression is pathologically lowered.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.